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Infection and Immunity, June 2003, p. 3663-3666, Vol. 71, No. 6
0019-9567/03/$08.00+0 DOI: 10.1128/IAI.71.6.3663-3666.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
Department of Internal Medicine, Inselspital,1 Department of Internal Medicine, Zieglerspital,2 Institute for Infectious Diseases, University of Bern, Bern,4 Department of Infectious Diseases, CHUV, Lausanne, Switzerland3
Received 25 July 2002/ Returned for modification 18 December 2002/ Accepted 19 March 2003
Intrathecal injections of 50 to 100 µg of (N-acetylmuramyl-L-alanyl-D-isoglutamine) muramyl dipeptide (MDP)/rabbit dose-dependently triggered tumor necrosis factor alpha (TNF-
) secretion (12 to 40,000 pg/ml) preceding the influx of leukocytes in the subarachnoid space of rabbits. Intrathecal instillation of heat-killed unencapsulated R6 pneumococci produced a comparable leukocyte influx but only a minimal level of preceding TNF-
secretion. The stereochemistry of the first amino acid (L-alanine) of the MDP played a crucial role with regard to its inflammatory potential. Isomers harboring D-alanine in first position did not induce TNF-
secretion and influx of leukocytes. This stereospecificity of MDPs was also confirmed by measuring TNF-
release from human peripheral mononuclear blood cells stimulated in vitro. These data show that the inflammatory potential of MDPs depends on the stereochemistry of the first amino acid of the peptide side chain and suggest that intact pneumococci and MDPs induce inflammation by different pathways.
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